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1.
Br J Nutr ; : 1-28, 2021 Feb 23.
Artigo em Inglês | MEDLINE | ID: mdl-33618785

RESUMO

Normal cardiac function is directly associated with the maintenance of cerebrovascular health. Whether the Mediterranean-Dietary Approach to Systolic Hypertension Intervention for Neurodegenerative Delay (MIND) diet, designed for the maintenance of neurocognitive health, is associated with cardiac remodeling is unknown. We evaluated 2512 Framingham Offspring Cohort participants who attended the 8th examination cycle and had available dietary and echocardiographic data (mean age 66 years; 55% women). Using multivariable regression, we related the cumulative MIND diet score (independent variable) to left ventricular (LV) ejection fraction, left atrial emptying fraction, LV mass (LVM), E/e' ratio (dependent variables; primary), global longitudinal strain, global circumferential strain (GCS), mitral annular plane systolic excursion, longitudinal segmental synchrony, LV hypertrophy, and aortic root diameter (secondary). Adjusting for age, sex, and energy intake, higher cumulative MIND diet scores were associated with lower values of indices of LV diastolic (E/e' ratio: logß=-0.03) and systolic function (GCS: ß=-0.04), and with higher values of LVM (logß=0.02), all P≤0.01. We observed effect modification by age in the association between the cumulative MIND diet score and GCS. When we further adjusted for clinical risk factors, the associations of the cumulative MIND diet score with GCS in participants ≥66 years (ß=-0.06, P=0.005) and LVM remained significant. In our community-based sample, relations between the cumulative MIND diet score and cardiac remodeling differ among indices of LV structure and function. Our results suggest that favorable associations between a higher cumulative MIND diet score and indices of LV function may be influenced by cardiometabolic and lifestyle risk factors.

2.
PLoS One ; 16(2): e0246355, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33592021

RESUMO

BACKGROUND: Lung function abnormalities are ubiquitous in heart failure (HF). It is unclear, however, if abnormal lung diffusion capacity is associated with cardiac remodeling and antedates HF. We hypothesized that lower lung diffusion capacity for carbon monoxide (DLCO) is associated with worse left ventricular (LV) systolic and diastolic function cross-sectionally, and with higher risk of HF prospectively. METHODS: We evaluated 2423 Framingham Study participants (mean age 66 years, 55% women) free of HF who underwent routine echocardiography and pulmonary function tests. We used multivariable regression models to relate DLCO, forced vital capacity (FVC), and forced expiratory volume in 1 second (FEV1) to left ventricular ejection fraction (LVEF), left atrial (LA) emptying fraction (LAEF), E/e', E/A, LV mass, and LA diameter (LAD). Multivariable-adjusted Cox proportional hazards regression was used to relate DLCO, FEV1, and FVC to incident HF. RESULTS: In multivariable-adjusted cross-sectional analyses, DLCO, FEV1, and FVC (dependent variables) were associated positively with LVEF (ßDLCO = 0.208, ßFEV1 = 0.021, and ßFVC = 0.025 per 5% increment in LVEF; p<0.005 for all), and LAEF (ßDLCO = 0.707, ßFEV1 = 0.058 and ßFVC = 0.058 per 5% increment in LAEF; p<0.002 for all). DLCO and FVC were inversely related to E/A (ßDLCO = -0.289, ßFVC = -0.047 per SD increment in E/A; p<0.001 for all). Additionally, DLCO, FEV1 and FVC were inversely related to HF risk (108 events, median follow-up 9.7 years; multivariable-adjusted hazard ratios per SD increment 0.90, 95% CI 0.86-0.95; 0.42, 95% CI 0.28-0.65, and 0.51, 95% CI 0.36-0.73, respectively). These results remained robust in analyses restricted to non-smokers. CONCLUSIONS: Our large community-based observations are consistent with the concept that lower lung diffusion capacity and expiratory flow rates are associated with cardiac remodeling and may antedate HF. Additional studies are needed to confirm our findings and to evaluate the prognostic utility of pulmonary function testing for predicting HF.

3.
JCI Insight ; 2021 Feb 16.
Artigo em Inglês | MEDLINE | ID: mdl-33591955

RESUMO

Recent advances in proteomic technologies have made high throughput profiling of low abundance proteins in large epidemiological cohorts increasingly feasible. We investigated whether aptamer-based proteomic profiling could identify biomarkers associated with future development of type 2 diabetes (T2DM) beyond known risk factors. We identified dozens of markers with highly significant associations with future T2DM across two large longitudinal cohorts (n=2,839) followed for up to 16 years. We leveraged proteomic, metabolomic, genetic and clinical data from humans to nominate one specific candidate to test for potential causal relationships in model systems. Our studies identified functional effects of aminoacylase 1 (ACY1), a top protein association with future T2DM risk, on amino acid metabolism and insulin homeostasis in vitro and in vivo. Further, a loss-of-function variant associated with circulating levels of the biomarker WAP, Kazal, immunoglobulin, Kunitz and NTR domain-containing protein 2 (WFIKKN2) was in turn associated with fasting glucose, hemoglobin A1c and HOMA-IR measurements in humans. In addition to identifying novel disease markers and potential pathways in T2DM, we provide publicly available data to be leveraged for new insights about gene function and disease pathogenesis in the context of human metabolism. .

4.
J Cardiovasc Magn Reson ; 23(1): 2, 2021 Jan 04.
Artigo em Inglês | MEDLINE | ID: mdl-33390171

RESUMO

BACKGROUND: The association of longitudinal trajectories of cardiovascular risk factors with cardiovascular magnetic resonance (CMR)-measures of cardiac structure and function in the community is not well known. Therefore we aimed to relate risk factor levels from different examination cycles to CMR-measures of the left ventricle (LV) and right ventricle in a population-based cohort. METHODS: We assessed conventional cardiovascular disease risk factors in 349 participants (143 women; aged 25-59 years) at three examination cycles (Exam 1 [baseline], at Exam 2 [7-years follow-up] and at Exam 3 [14-years follow-up]) of the KORA S4 cohort and related single-point measurements of individual risk factors and longitudinal trajectories of these risk factors to various CMR-measures obtained at Exam 3. RESULTS: High levels of diastolic blood pressure, waist circumference, and LDL-cholesterol at the individual exams were associated with worse cardiac function and structure. Trajectory clusters representing higher levels of the individual risk factors were associated with worse cardiac function and structure compared to low risk trajectory clusters of individual risk factors. Multivariable (combining different risk factors) trajectory clusters were associated with different cardiac parameters in a graded fashion (e.g. decrease of LV stroke volume for middle risk cluster ß = - 4.91 ml/m2, 95% CI - 7.89; - 1.94, p < 0.01 and high risk cluster ß = - 7.00 ml/m2, 95% CI - 10.73; - 3.28, p < 0.001 compared to the low risk cluster). The multivariable longitudinal trajectory clusters added significantly to explain variation in CMR traits beyond the multivariable risk profile obtained at Exam 3. CONCLUSIONS: Cardiovascular disease risk factor levels, measured over a time period of 14 years, were associated with CMR-derived measures of cardiac structure and function. Longitudinal multivariable trajectory clusters explained a greater proportion of the inter-individual variation in cardiac traits than multiple risk factor assessed contemporaneous with the CMR exam.

5.
Circ Heart Fail ; 14(1): e007275, 2021 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-33464957

RESUMO

BACKGROUND: Heart failure (HF) is a heterogeneous disease characterized by significant metabolic disturbances; however, the breadth of metabolic dysfunction before the onset of overt disease is not well understood. The purpose of this study was to determine the association of circulating metabolites with incident HF to uncover novel metabolic pathways to disease. METHODS: We performed targeted plasma metabolomic profiling in a deeply phenotyped group of Black adults from the JHS (Jackson Heart Study; n=2199). We related metabolites associated with incident HF to established etiological mechanisms, including increased left ventricular mass index and incident coronary heart disease. Furthermore, we evaluated differential associations of metabolites with HF with preserved ejection fraction versus HF with reduced ejection fraction. RESULTS: Metabolites associated with incident HF included products of posttranscriptional modifications of RNA, as well as polyamine and nitric oxide metabolism. A subset of metabolite-HF associations was independent of well-established HF pathways such as increased left ventricular mass index and incident coronary heart disease and included homoarginine (per 1 SD increase in metabolite level, hazard ratio, 0.77; P=1.2×10-3), diacetylspermine (hazard ratio, 1.34; P=3.4×10-3), and uridine (hazard ratio, 0.79; P, 3×10-4). Furthermore, metabolites involved in pyrimidine metabolism (orotic acid) and collagen turnover (N-methylproline) among others were part of a distinct metabolic signature that differentiated individuals with HF with preserved ejection fraction versus HF with reduced ejection fraction. CONCLUSIONS: The integration of clinical phenotyping with plasma metabolomic profiling uncovered novel metabolic processes in nontraditional disease pathways underlying the heterogeneity of HF development in Black adults.

6.
Nat Commun ; 12(1): 715, 2021 01 29.
Artigo em Inglês | MEDLINE | ID: mdl-33514711

RESUMO

Coronary artery calcium is an accurate predictor of cardiovascular events. While it is visible on all computed tomography (CT) scans of the chest, this information is not routinely quantified as it requires expertise, time, and specialized equipment. Here, we show a robust and time-efficient deep learning system to automatically quantify coronary calcium on routine cardiac-gated and non-gated CT. As we evaluate in 20,084 individuals from distinct asymptomatic (Framingham Heart Study, NLST) and stable and acute chest pain (PROMISE, ROMICAT-II) cohorts, the automated score is a strong predictor of cardiovascular events, independent of risk factors (multivariable-adjusted hazard ratios up to 4.3), shows high correlation with manual quantification, and robust test-retest reliability. Our results demonstrate the clinical value of a deep learning system for the automated prediction of cardiovascular events. Implementation into clinical practice would address the unmet need of automating proven imaging biomarkers to guide management and improve population health.


Assuntos
Doenças Cardiovasculares/epidemiologia , Dor no Peito/diagnóstico , Vasos Coronários/diagnóstico por imagem , Aprendizado Profundo , Processamento de Imagem Assistida por Computador/métodos , Idoso , Doenças Assintomáticas , Cálcio/análise , Doenças Cardiovasculares/complicações , Doenças Cardiovasculares/diagnóstico , Doenças Cardiovasculares/patologia , Dor no Peito/etiologia , Vasos Coronários/patologia , Feminino , Seguimentos , Humanos , Masculino , Pessoa de Meia-Idade , Reprodutibilidade dos Testes , Estudos Retrospectivos , Medição de Risco/métodos , Tomografia Computadorizada por Raios X
7.
Int J Cardiol ; 2021 Jan 07.
Artigo em Inglês | MEDLINE | ID: mdl-33422565

RESUMO

BACKGROUND AND AIMS: Cardiac and vascular growth factors (GF) may influence myocardial remodeling through cardiac growth and angiogenic effects. We hypothesized that concentrations of circulating GF are associated with cardiac remodeling traits. METHODS: We related blood concentrations of vascular endothelial GF (VEGF), VEGFR-1 (sFlt1), angiopoietin 2 (Ang-2), soluble angiopoietin type-2 receptor (sTie2), hepatocyte GF (HGF), insulin-like GF (IGF)-1, IGF binding protein (IGFBP)-3, and growth differentiation factor-15 (GDF-15) to echocardiographic traits in 3151 Framingham Study participants (mean age 40 years, 55% women). We evaluated the following measures: left ventricular (LV) mass index (LVMi), LV ejection fraction (LVEF), global longitudinal strain (GLS), mitral E/e', and aortic root diameter (AoR). All biomarker values were sex-standardized. RESULTS: In multivariable-adjusted analyses, higher GDF-15 concentrations were associated with higher log-LVMi (ß = 0.009 per SD, P = 0.01). Similarly, sTie2 concentrations were positively associated with log-E/e' (ß = 0.011 per SD, P = 0.04). IGF-1 and Ang-2 concentrations were positively and negatively associated with GLS, respectively (ßIGF-1 = 0.16 per SD and ßAng-2 = -0.15 per SD, both P < 0.05), whereas higher sFlt1 and Ang-2 levels were associated with smaller log-AoR (ßsFlt1 = -0.004 per SD and ß Ang-2 = -0.005 per SD, respectively; P < 0.05). CONCLUSION: In our large community-based sample, we observed patterns of associations between several circulating vascular GF and cardiac remodeling indices that are consistent with the known biological effects of these pro- and anti-angiogenic factors on the myocardium and conduit arteries. Additional studies are warranted to replicate our findings and assess their prognostic significance.

8.
Circ Res ; 128(2): 287-303, 2021 Jan 22.
Artigo em Inglês | MEDLINE | ID: mdl-33476202

RESUMO

Atherosclerotic cardiovascular disease (ASCVD) proceeds through a series of stages: initiation, progression (or regression), and complications. By integrating known biology regarding molecular signatures of each stage with recent advances in high-dimensional molecular data acquisition platforms (to assay the genome, epigenome, transcriptome, proteome, metabolome, and gut microbiome), snapshots of each phase of atherosclerotic cardiovascular disease development can be captured. In this review, we will summarize emerging approaches for assessment of atherosclerotic cardiovascular disease risk in humans using peripheral blood molecular signatures and molecular imaging approaches. We will then discuss the potential (and challenges) for these snapshots to be integrated into a personalized movie providing dynamic readouts of an individual's atherosclerotic cardiovascular disease risk status throughout the life course.

9.
Hypertension ; 77(2): 338-346, 2021 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-33390053

RESUMO

Intrinsic frequencies (IFs) derived from arterial waveforms are associated with cardiovascular performance, aging, and prevalent cardiovascular disease (CVD). However, prognostic value of these novel measures is unknown. We hypothesized that IFs are associated with incident CVD risk. Our sample was drawn from the Framingham Heart Study Original, Offspring, and Third Generation Cohorts and included participants free of CVD at baseline (N=4700; mean age 52 years, 55% women). We extracted 2 dominant frequencies directly from a series of carotid pressure waves: the IF of the coupled heart and vascular system during systole (ω1) and the IF of the decoupled vasculature during diastole (ω2). Total frequency variation (Δω) was defined as the difference between ω1 and ω2. We used Cox proportional hazards regression models to relate IFs to incident CVD events during a mean follow-up of 10.6 years. In multivariable models adjusted for CVD risk factors, higher ω1 (hazard ratio [HR], 1.14 [95% CI], 1.03-1.26]; P=0.01) and Δω (HR, 1.16 [95% CI, 1.03-1.30]; P=0.02) but lower ω2 (HR, 0.87 [95% CI, 0.77-0.99]; P=0.03) were associated with higher risk for incident composite CVD events. In similarly adjusted models, higher ω1 (HR, 1.23 [95% CI, 1.07-1.42]; P=0.004) and Δω (HR, 1.26 [95% CI, 1.05-1.50]; P=0.01) but lower ω2 (HR, 0.81 [95% CI, 0.66-0.99]; P=0.04) were associated with higher risk for incident heart failure. IFs were not significantly associated with incident myocardial infarction or stroke. Novel IFs may represent valuable markers of heart failure risk in the community.

10.
J Bone Miner Res ; 2021 Jan 12.
Artigo em Inglês | MEDLINE | ID: mdl-33434288

RESUMO

Osteoporosis, a disease characterized by low bone mineral density (BMD), increases the risk for fractures. Conventional risk factors alone do not completely explain measured BMD or osteoporotic fracture risk. Metabolomics may provide additional information. We aim to identify BMD-associated metabolomic markers that are predictive of fracture risk. We assessed 209 plasma metabolites by liquid chromatography with tandem mass spectrometry (LC-MS/MS) in 1552 Framingham Offspring Study participants, and measured femoral neck (FN) and lumbar spine (LS) BMD 2 to 10 years later using dual-energy X-ray absorptiometry. We assessed osteoporotic fractures up to 27-year follow-up after metabolomic profiling. We identified 27 metabolites associated with FN-BMD or LS-BMD by LASSO regression with internal validation. Incorporating selected metabolites significantly improved the prediction and the classification of osteoporotic fracture risk beyond conventional risk factors (area under the curve [AUC] = 0.74 for the model with identified metabolites and risk factors versus AUC = 0.70 with risk factors alone, p = .001; net reclassification index = 0.07, p = .03). We replicated significant improvement in fracture prediction by incorporating selected metabolites in 634 participants from the Hong Kong Osteoporosis Study (HKOS). The glycine, serine, and threonine metabolism pathway (including four identified metabolites: creatine, dimethylglycine, glycine, and serine) was significantly enriched (false discovery rate [FDR] p value = .028). Furthermore, three causally related metabolites (glycine, phosphatidylcholine [PC], and triacylglycerol [TAG]) were negatively associated with FN-BMD, whereas PC and TAG were negatively associated with LS-BMD through Mendelian randomization analysis. In summary, metabolites associated with BMD are helpful in osteoporotic fracture risk prediction. Potential causal mechanisms explaining the three metabolites on BMD are worthy of further experimental validation. Our findings may provide novel insights into the pathogenesis of osteoporosis. © 2021 American Society for Bone and Mineral Research (ASBMR).

12.
J Am Heart Assoc ; 10(1): e018020, 2021 Jan 05.
Artigo em Inglês | MEDLINE | ID: mdl-33372532

RESUMO

Background Proteomic biomarkers related to cardiovascular disease risk factors may offer insights into the pathogenesis of cardiovascular disease. We investigated whether modifiable lifestyle risk factors for cardiovascular disease are associated with distinctive proteomic signatures. Methods and Results We analyzed 1305 circulating plasma proteomic biomarkers (assayed using the SomaLogic platform) in 897 FHS (Framingham Heart Study) Generation 3 participants (mean age 46±8 years; 56% women; discovery sample) and 1121 FOS (Framingham Offspring Study) participants (mean age 52 years; 54% women; validation sample). Participants were free of hypertension, diabetes mellitus, and clinical cardiovascular disease. We used linear mixed effects models (adjusting for age, sex, body mass index, and family structure) to relate levels of each inverse-log transformed protein to 3 lifestyle factors (ie, smoking, alcohol consumption, and physical activity). A Bonferroni-adjusted P value indicated statistical significance (based on number of proteins and traits tested, P<4.2×10-6 in the discovery sample; P<6.85×10-4 in the validation sample). We observed statistically significant associations of 60 proteins with smoking (37/40 top proteins validated in FOS), 30 proteins with alcohol consumption (23/30 proteins validated), and 5 proteins with physical activity (2/3 proteins associated with the physical activity index validated). We assessed the associations of protein concentrations with previously identified genetic variants (protein quantitative trait loci) linked to lifestyle-related disease traits in the genome-wide-association study catalogue. The protein quantitative trait loci were associated with coronary artery disease, inflammation, and age-related mortality. Conclusions Our cross-sectional study from a community-based sample elucidated distinctive sets of proteins associated with 3 key lifestyle factors.

14.
Neurology ; 2020 Dec 02.
Artigo em Inglês | MEDLINE | ID: mdl-33268560

RESUMO

OBJECTIVE: To conduct a comprehensive analysis of circulating metabolites and incident stroke in large prospective population-based settings. METHODS: We investigated the association of metabolites with risk of stroke in seven prospective cohort studies including 1,791 incident stroke events among 38,797 participants in whom circulating metabolites were measured by Nuclear Magnetic Resonance (1H-NMR) technology. The relationship between metabolites and stroke was assessed using Cox proportional hazards regression models. The analyses were performed considering all incident stroke events and ischemic and hemorrhagic events separately. RESULTS: The analyses revealed ten significant metabolite associations. Amino acid histidine (hazard ratio (HR) per standard deviation (SD) = 0.90, 95% confidence interval (CI): 0.85, 0.94; P = 4.45×10-5), glycolysis-related metabolite pyruvate (HR per SD = 1.09, 95% CI: 1.04, 1.14; P = 7.45×10-4), acute phase reaction marker glycoprotein acetyls (HR per SD = 1.09, 95% CI: 1.03, 1.15; P = 1.27×10-3), cholesterol in high-density lipoprotein (HDL) 2 and several other lipoprotein particles were associated with risk of stroke. When focusing on incident ischemic stroke, a significant association was observed with phenylalanine (HR per SD = 1.12, 95% CI: 1.05, 1.19; P = 4.13×10-4) and total and free cholesterol in large HDL particles. CONCLUSIONS: We found association of amino acids, glycolysis-related metabolites, acute phase reaction markers, and several lipoprotein subfractions with the risk of stroke. These findings support the potential of metabolomics to provide new insights into the metabolic changes preceding stroke.

15.
PLoS One ; 15(12): e0243199, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33301464

RESUMO

INTRODUCTION: Obesity, hypertension, and diabetes are independently associated with cardiac remodeling and frequently co-cluster. The conjoint and separate influences of these conditions on cardiac remodeling have not been investigated. MATERIALS AND METHODS: We evaluated 5,741 Framingham Study participants (mean age 50 years, 55% women) who underwent echocardiographic measurements of left ventricular (LV) mass (LVM), LV ejection fraction (LVEF), global longitudinal strain (GLS), mitral E/e', left atrial end-systolic (peak) dimension (LASD) and emptying fraction (LAEF). We used multivariable generalized linear models to estimate the adjusted-least square means of these measures according to cross-classified categories of body mass index (BMI; normal, overweight and obese), hypertension (yes/no), and diabetes (yes/no). RESULTS: We observed statistically significant interactions of BMI category, hypertension, and diabetes with LVM, LVEF, GLS, and LAEF (p for all 3-way interactions <0.01). Overweight and obesity (compared to normal BMI), hypertension, and diabetes status were individually and conjointly associated with higher LVM and worse GLS (p<0.01 for all). We observed an increase of 34% for LVM and of 9% for GLS between individuals with a normal BMI and without hypertension or diabetes compared to obese individuals with hypertension and diabetes. Presence of hypertension was associated with higher LVEF, whereas people with diabetes had lower LVEF. CONCLUSIONS: Obesity, hypertension, and diabetes interact synergistically to influence cardiac remodeling. These findings may explain the markedly heightened risk of heart failure and cardiovascular disease when these factors co-cluster.

16.
Nat Commun ; 11(1): 6417, 2020 12 18.
Artigo em Inglês | MEDLINE | ID: mdl-33339817

RESUMO

Pharmaceutical drugs targeting dyslipidemia and cardiovascular disease (CVD) may increase the risk of fatty liver disease and other metabolic disorders. To identify potential novel CVD drug targets without these adverse effects, we perform genome-wide analyses of participants in the HUNT Study in Norway (n = 69,479) to search for protein-altering variants with beneficial impact on quantitative blood traits related to cardiovascular disease, but without detrimental impact on liver function. We identify 76 (11 previously unreported) presumed causal protein-altering variants associated with one or more CVD- or liver-related blood traits. Nine of the variants are predicted to result in loss-of-function of the protein. This includes ZNF529:p.K405X, which is associated with decreased low-density-lipoprotein (LDL) cholesterol (P = 1.3 × 10-8) without being associated with liver enzymes or non-fasting blood glucose. Silencing of ZNF529 in human hepatoma cells results in upregulation of LDL receptor and increased LDL uptake in the cells. This suggests that inhibition of ZNF529 or its gene product should be prioritized as a novel candidate drug target for treating dyslipidemia and associated CVD.


Assuntos
Doenças Cardiovasculares/genética , Genoma Humano , Mutação com Perda de Função/genética , Terapia de Alvo Molecular , Bancos de Espécimes Biológicos , Doenças Cardiovasculares/sangue , Inativação Gênica , Marcação de Genes , Estudo de Associação Genômica Ampla , Humanos , Lipídeos/sangue , Fígado/metabolismo , Fenômica , Receptores de LDL/genética , Reino Unido
17.
Soc Sci Med ; 268: 113443, 2020 Oct 23.
Artigo em Inglês | MEDLINE | ID: mdl-33137680

RESUMO

Rural-urban differences in morbidity and mortality across the United States have been well documented and termed the "rural mortality penalty". However, research studies frequently treat rural areas as homogeneous and often do not account for geospatial variability in rural health risks by both county, state, region, race, and sex within the United States. Additionally, people living in the rural South of the US have higher rates of morbidity and mortality compared to both their urban counterparts and other rural areas. Of those living in southern rural communities, people of color experience higher rates of death and disease compared to white populations. Although there is a wealth of research that uses individual-level behaviors to explain rural-urban health disparities, there is less focus on how community and structural factors influence these differences. This review focuses on the "southern rural health penalty", a term coined by the authors, which refers to the high rate of mortality and morbidity in southern rural areas in the USA compared to both urban areas and non-southern rural places. We use macrosocial determinants of health to explain possible reasons for the "southern rural health penalty". This review can guide future research on rural health between southern and non-southern populations in the US and examine if macrosocial determinants of health can explain health disparities within southern rural populations.

19.
Br J Sports Med ; 54(24): 1499-1506, 2020 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-33239356

RESUMO

OBJECTIVES: To examine the joint associations of accelerometer-measured physical activity and sedentary time with all-cause mortality. METHODS: We conducted a harmonised meta-analysis including nine prospective cohort studies from four countries. 44 370 men and women were followed for 4.0 to 14.5 years during which 3451 participants died (7.8% mortality rate). Associations between different combinations of moderate-to-vigorous intensity physical activity (MVPA) and sedentary time were analysed at study level using Cox proportional hazards regression analysis and summarised using random effects meta-analysis. RESULTS: Across cohorts, the average time spent sedentary ranged from 8.5 hours/day to 10.5 hours/day and 8 min/day to 35 min/day for MVPA. Compared with the referent group (highest physical activity/lowest sedentary time), the risk of death increased with lower levels of MVPA and greater amounts of sedentary time. Among those in the highest third of MVPA, the risk of death was not statistically different from the referent for those in the middle (16%; 95% CI 0.87% to 1.54%) and highest (40%; 95% CI 0.87% to 2.26%) thirds of sedentary time. Those in the lowest third of MVPA had a greater risk of death in all combinations with sedentary time; 65% (95% CI 1.25% to 2.19%), 65% (95% CI 1.24% to 2.21%) and 263% (95% CI 1.93% to 3.57%), respectively. CONCLUSION: Higher sedentary time is associated with higher mortality in less active individuals when measured by accelerometry. About 30-40 min of MVPA per day attenuate the association between sedentary time and risk of death, which is lower than previous estimates from self-reported data.

20.
J Am Heart Assoc ; 9(21): e016762, 2020 Nov 03.
Artigo em Inglês | MEDLINE | ID: mdl-33100134

RESUMO

Background Exhaled carbon monoxide (eCO) is directly associated with traditional cardiovascular disease risk factors and incident cardiovascular disease. However, its relation with the cardiovascular health score and incidence of heart failure (HF) has not been investigated. Methods and Results We measured eCO in 3521 Framingham Heart Study Offspring participants attending examination cycle 6 (mean age 59 years, 53% women). We related the cardiovascular health score (composite of blood pressure, fasting plasma glucose, total cholesterol, body mass index, smoking, diet, and physical activity) to eCO adjusting for age, sex, and smoking. Higher cardiovascular health scores were associated with lower eCO (ß=-0.02, P<0.0001), even among nonsmokers. Additionally, C-reactive protein, plasminogen activator inhibitor-1, fibrinogen, growth differentiation factor-15, homocysteine, and asymmetrical dimethylarginine were positively associated with eCO (P≤0.003 for all). The age- and sex-adjusted and multivariable-adjusted heritabilities of eCO were 49.5% and 31.4%, respectively. Over a median follow-up of 18 years, 309 participants (45% women) developed HF. After multivariable adjustment, higher eCO was associated with higher risk of HF (hazards ratio per SD increment: 1.39; 95% CI, 1.19-1.62 [P<0.001]) and with higher risk of HF with reduced ejection fraction (N=144 events; hazard ratio per SD increment in eCO: 1.43; 95% CI, 1.15-1.77 [P=0.001]). Conclusions In our community-based sample, higher levels of eCO were associated with lower cardiovascular health scores, an adverse cardiovascular biomarker profile, and a higher risk of HF, specifically HF with reduced ejection fraction. Our findings suggest that carbon monoxide may identify a novel pathway to HF development.

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